The Sorbitol Pathway: Enzyme Localization and Content in Normal and Diabetic Nerve and Cord

The enzymes of the sorbitol pathway, aldose reductase and sorbitol dehydrogenase, were investigated in sciatic nerve and spinal cord. The substrate specificities of spinal cord aldose reductase indicates that it is a variant of TPN L-hexonate dehydrogenase which possesses poor polyol forming ability. In contrast, the cauda equina and sciatic nerve aldose reductase have a true aldose reductase with considerable polyol forming ability. The distribution of the latter enzyme is associated with the presence of Schwann cells. Wallerian degeneration experiments are compatible with the localization of true aldose reductase in the Schwann cell and sorbitol dehydrogenase in the axon. There was no change in the levels of sorbitol dehydrogenase in diabetic nerves, a 30 per cent decrease occurred in the aldose reductase content. This decrease suggests a metabolic abnormality of the Sehwann cell, possibly resulting from alrered cellular integrity, which may have important implication for the otiology of diabetic neuropathy.